The (GT)n polymorphism and haplotype of the COL1A2 gene, but not the (AAAG)n polymorphism of the PTHR1 gene, are associated with bone mineral density in Chinese.

Collagen type I alpha2 (COL1A2) and parathyroid hormone (PTH)/PTH-related peptide receptor (PTHR1) are two prominent candidate genes for bone mineral density (BMD). To test their importance for BMD variation in Chinese, we recruited 388 nuclear families composed of both parents and at least one healthy daughter with a total of 1,220 individuals, and simultaneously analyzed population stratification, total-family association, and within-family association between BMD at the spine and hip and the (GT)n marker in the intron 1 of the COL1A2 gene and the (AAAG)n marker in the P3 promoter of PTHR1 gene. We also performed these association analyses with haplotypes of the MspI and (GT)n polymorphisms in the COL1A2 gene.

The -1997 G/T polymorphism in the COLIA1 upstream regulatory region is associated with hip bone mineral density (BMD) in Chinese nuclear families.

Type I collagen is the most abundant protein of bone matrix, and the collagen type I alpha 1(COLIA1) gene has been considered one of the most important candidate genes for osteoporosis. In this study, we simultaneously tested linkage and/or association of the -1997 G/T polymorphism in the COLIA1 upstream regulatory region with the variation of bone mineral density (BMD) in 1263 subjects from 402 Chinese nuclear families, consisted of both parents and at least one healthy female offspring from 20 to 45 years of age. All the subjects were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

APOE haplotypes influence bone mineral density in Caucasian males but not females.

Low bone mineral density (BMD) is one of the most important risk factors for osteoporosis. Apolipoprotein E (APOE) has been considered as a candidate gene for osteoporosis because of its influence on osteoblast uptake of lipoprotein-borne vitamin K. Using the quantitative transmission disequilibrium test QTDT, we examined linkage and/or association of APOE and BMD at the lumbar spine and the total hip in a sample of 387 Caucasian nuclear families with 715 parents and 953 children.

[A986S polymorphism of calcium-sensing receptor gene is not related to bone mineral density or bone size in premenopausal Chinese women].

Objective: To investigate the association of a calcium-sensing receptor (CaSR) gene missense polymorphism, 986Ala/Ser (A986S), with bone mineral density (BMD) and bone size in healthy Chinese premenopausal women.

Methods: A total of 285 healthy Chinese premenopausal women (20.0 to 41.

Genetic dissection of human stature in a large sample of multiplex pedigrees.

Recently, we reported a whole genome scan on a sample of 630 Caucasian subjects from 53 human pedigrees. Several genomic regions were suggested to be linked to height. In an attempt to confirm the identified genomic regions, as well as to identify new genomic regions linked to height, we conducted a whole genome linkage study on an extended sample of 1,816 subjects from 79 pedigrees, which includes the 53 pedigrees containing the original 630 subjects from our previous whole genome study and an additional 128 new subjects, and 26 further pedigrees containing 1,058 subjects.

SNPP: automating large-scale SNP genotype data management.

Unlabelled: To manage high-throughput single nucleotide polymorphism (SNP) genotyping data efficiently, we developed a dynamic general database management system-SNPP (SNP Processor). It provides several functions, including data importing with comparison, Mendelian inheritance check within pedigrees, data compiling and exporting. Furthermore, SNPP may generate files for repeat genotyping and transform them into files that can be executed by a liquid handling system.

Quantifying the relationship between gene expressions and trait values in general pedigrees.

Treating mRNA transcript abundances as quantitative traits and examining their relationships with clinical traits have been pursued by using an analytical approach of quantitative genetics. Recently, Kraft et al. presented a family expression association test (FEXAT) for correlation between gene expressions and trait values with a family-based (sibships) design.

A follow-up linkage study for bone size variation in an extended sample.

Bone size, which has strong genetic determination, is an important determinant of bone strength and a risk factor of osteoporotic fractures. We previously reported an approximately 10-cm genome-wide linkage scan in 630 subjects from 53 US Caucasian pedigrees. The strongest evidence of linkage was obtained on chromosome 17q22 near the marker D17S787, with a two-point LOD score of 3.

Test of linkage and/or association between the estrogen receptor alpha gene with bone mineral density in Caucasian nuclear families.

Extensive studies have been performed on the association between the estrogen receptor alpha (ER-alpha) gene and bone mineral density (BMD). Despite considerable efforts, the studies using limited markers and relatively small sample size have yielded largely inconsistent results. In this study, 1873 Caucasian subjects from 405 nuclear families containing 1512 sib pairs were recruited.

[Preliminary linkage analysis of a Chinese family with benign familial infantile convulsion].

Objective: Benign familial infantile convulsions (BFIC) is a recently recognized autosomal dominant inherited disorder. This epileptic syndrome typically begins between 3 and 12 months of age with clusters of partial seizures in most cases and carries a good prognosis. So far, three loci have been linked to chromosome 19q12.

Tests of linkage and/or association of TGF-beta1 and COL1A1 genes with bone mass.

Transforming growth factor beta 1 (TGF-beta1) is involved in bone metabolism and collagen type I alpha 1 (COL1A1) is the most abundant protein of bone matrix. Both have been considered as candidate genes for osteoporosis. In this study, we employed the transmission disequilibrium test (TDT) to examine the relationship between each of the two genes with bone mineral density (BMD) and bone mineral content (BMC) at the spine and hip in a sample of 1668 subjects from 387 Caucasian nuclear families.

Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes.

Background: The adequacy of association studies for complex diseases depends critically on the existence of linkage disequilibrium (LD) between functional alleles and surrounding SNP markers.

Results: We examined the patterns of LD and haplotype distribution in eight candidate genes for osteoporosis and/or obesity using 31 SNPs in 1,873 subjects. These eight genes are apolipoprotein E (APOE), type I collagen alpha1 (COL1A1), estrogen receptor-alpha (ER-alpha), leptin receptor (LEPR), parathyroid hormone (PTH)/PTH-related peptide receptor type 1 (PTHR1), transforming growth factor-beta1 (TGF-beta1), uncoupling protein 3 (UCP3), and vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR).

Genetics of bone mineral density: evidence for a major pleiotropic effect from an intercontinental study.

Unlabelled: BMD is a primary predictor of osteoporotic fracture, and its genetic determination is still unclear. This study showed that the correlation between BMD at different skeletal sites is caused by an underlying genetic structure of common genetic effects. In addition to possible shared (pleiotropic) genetic and environmental effects, each of the BMD variables may also be determined by site-specific genetic factors.

Current limitations of SNP data from the public domain for studies of complex disorders: a test for ten candidate genes for obesity and osteoporosis.

Background: Public SNP databases are frequently used to choose SNPs for candidate genes in the association and linkage studies of complex disorders. However, their utility for such studies of diseases with ethnic-dependent background has never been evaluated.

Results: To estimate the accuracy and completeness of SNP public databases, we analyzed the allele frequencies of 41 SNPs in 10 candidate genes for obesity and/or osteoporosis in a large American-Caucasian sample (1,873 individuals from 405 nuclear families) by PCR-invader assay.

Lack of association between the HindIII RFLP of the osteocalcin (BGP) gene and bone mineral density (BMD) in healthy pre- and postmenopausal Chinese women.

In Caucasian populations, the polymorphic restriction endonuclease HindIII marker of the osteocalcin (also known as BGP, for bone Gla protein) gene has recently been reported to be associated with bone mass, a major risk determinant of osteoporosis. In this study, we investigated the relationship between the BGP HindIII polymorphism and bone mineral density (BMD) in 388 premenopausal (31.18 +/- 5.

Genome scan for QTLs underlying bone size variation at 10 refined skeletal sites: genetic heterogeneity and the significance of phenotype refinement.

To identify quantitative trait loci (QTLs) underlying variation in bone size, we conducted a whole-genome linkage scan in 53 pedigrees with 630 subjects using 380 microsatellite markers. Lumbar area 1, 2, 3, and 4 at the spine, femoral neck, trochanter, intertrochanter areas at the hip, ultradistal, mid-distal, and one-third distal areas at the wrist were measured by dual-energy X-ray absorptiometry (DXA), and adjusted for age, height, weight, and sex. Two-point and multipoint linkage analyses were performed for skeletal bone size at each site and their composite measurements using the SOLAR package.

Robust indices of Hardy-Weinberg disequilibrium for QTL fine mapping.

Hardy-Weinberg disequilibrium (HWD) measures have been proposed using dense markers to fine map a quantitative trait locus (QTL) to regions < approximately 1 cM. Earlier HWD measures may introduce bias in the fine mapping because they are dependent on marker allele frequencies across loci. Hence, HWD indices that do not depend on marker allele frequencies are desired for fine mapping.

Structure and molecular phylogeny of sasA genes in cyanobacteria: insights into evolution of the prokaryotic circadian system.

Cyanobacteria are the simplest organisms known to have a circadian system. In addition to the three well-studied kai genes, kaiA, kaiB, and kaiC, an important element of this system is a two-component sensory transduction histidine kinase sasA. Using publicly available data of complete prokaryotic genomes, we performed structural and phylogenetic analyses of the sasA genes.

A major gene model of adult height is suggested in Chinese.

Adult height (stature), as a complex quantitative trait, has been studied in different populations. However, few genetic studies on height were performed on the Chinese, the largest population in the world. In this study, familial correlation and segregation analyses were carried out for adult height in a Chinese sample composed of 385 nuclear families with a total of 1,169 informative individuals.

Tests of linkage and/or association of the LEPR gene polymorphisms with obesity phenotypes in Caucasian nuclear families.

Genetic variations in the leptin receptor (LEPR) gene have been conceived to affect body weight in general populations. In this study, using the tests implemented in the statistical package QTDT, we evaluated association and/or linkage of the LEPR gene with obesity phenotypes in a large sample comprising 1,873 subjects from 405 Caucasian nuclear families. Obesity phenotypes tested include body mass index (BMI), fat mass, percentage fat mass (PFM), and lean mass, with the latter three measured by dual-energy X-ray absorptiometry (DXA).

A follow-up linkage study for quantitative trait loci contributing to obesity-related phenotypes.

We have recently reported a whole-genome scan in a sample of 630 subjects from 53 extended pedigrees, in which several genomic regions that may contain quantitative trait loci (QTLs) for obesity were suggested. In the present study, with an attempt to confirm our previous findings, we performed a follow-up linkage study in an expanded sample of 79 pedigrees with 1816 subjects (including expanded previous 53 pedigrees and 26 newly recruited pedigrees containing 1058 subjects). A new set of microsatellite markers spanning previously identified regions were selected, with the average genomic distance narrowed from approximately 10 cM to approximately 5 cM in this study.

High heritability of bone size at the hip and spine in Chinese.

Bone size, an independent determinant of bone strength, is an important risk factor for osteoporotic fracture. In the present study, we investigated the magnitude of the genetic determination of bone size at the spine and hip and their genetic covariation (if any) in a population of Chinese residing in Shanghai City of P.R.

Association between COL1A1 gene polymorphisms and bone size in Caucasians.

Bone size is an important determinant of bone strength and a risk factor of osteoporotic fracture. Several studies indicate that bone size has a high heritability. Thus, a better understanding of genetic factors regulating bone size might have important clinical implications.

Bone mineral density in elderly Chinese: effects of age, sex, weight, height, and body mass index.

To enhance our understanding of the relationship between bone mineral density (BMD) and sex, age, body mass index (BMI), weight, and height in elderly Chinese, we studied 258 males aged 50-80 years (mean +/- SD, 62.9 +/- 6.2 years) and 193 females aged 46-75 years (59.

Evidence for a major gene underlying bone size variation in the Chinese.

Osteoporosis is a major public health problem defined as a loss of bone strength, of which bone size is an important determinant. In the present study, familial correlation and segregation analyses for the spine and hip bone sizes were performed for the first time in a Chinese sample composed of 393 nuclear families with a total of 1,193 individuals. The results indicate a major gene of codominant inheritance for spine bone size; however, there is no evidence of a major gene influencing hip bone size.